Ben Shen, PhD

Chair
Professor
Director, Natural Products Discovery Center at Scripps Research
Department of Chemistry
Florida Campus


 Email

Scripps Research Joint Appointments

Professor, Department of Molecular Medicine
Professor, Worm Institute for Research and Medicine (WIRM)
Faculty, Graduate Program

Research Focus

Natural Product Biosynthesis, Engineering, and Drug Discovery.  Microorganisms produce a large variety of biologically active substances representing a vast diversity of fascinating molecular architecture not available in any other systems. Our research centers on the chemistry, biochemistry and genetics of the biosynthesis of these secondary metabolites. Blending organic chemistry, biochemistry, and molecular biology, we take a multidisciplinary approach to study the secondary metabolism by asking the following questions: what reactions are available in nature, what are the enzymatic mechanisms of these reactions, how are these reactions linked to produce complex structures, what are the regulatory mechanisms of these pathways, and, ultimately, how can we leverage a large microbial strain collection and develop enabling genome mining and synthetic biology technologies for natural product discovery and production, and manipulate nature's biosynthetic machinery for the discovery and development of new drugs. Members of our group gain broad training spanning organic chemistry, biochemistry, microbiology and molecular biology, a qualification that is becoming essential for the modern bioorganic chemists who seek career opportunity in both academia and pharmaceutical and biotechnology industry (http://www.scripps.edu/shen/).

Natural Products Discovery Center at Scripps Research.  Natural products are significantly underrepresented in current small molecule libraries.  The current Natural Products Library (NPL) at Scripps Research's Natural Product Discovery Center consists of: (i) purified natural products with fully assigned structures, (b) MPLC (on C-18 semipreparative column) fractions, and (c) crude extracts.  The NPL is presented in 384-well format with all materials dissolved in DMSO (1 mM for pure compounds and 50 mg/mL for fractions and extracts), compatible with most of the HTS platforms.  The NPL currently available for screening includes: (a) ~600 pure natural products, (b) ~53,500 MPLC fractions, (c) ~205,000 crude extracts.  The NPL provides an unprecedented molecular diversity to screen emerging targets for drug leads, and selected members of the NPL serves as outstanding small molecule probes to interrogate biology.  Central to the Natural Products Discovery Center is the large microbial strain collection, containing a total of 217,352 bacterial and fungal strains, of which 62,328 are actinobacteria, 14,465 other bacteria, 92,225 fungi, and 48,334 unidentified (bacteria or fungi).  Promising leads could therefore be produced in sufficient quantities by microbial fermentation for follow up studies and, ultimately, clinical development (http://www.scripps.edu/shen/NPLI/npliattsri.html).


Education

Ph.D. (Organic Chemistry and Biochemistry), Oregon State University, 1991
M.S. (Chemistry), Chinese Academy of Sciences, 1984
B.S. (Chemistry), Hangzhou University, 1982

Professional Experience

2011-2017 Professor (Joint Appointment), Molecular Therapeutics, Scripps Research
2005-2010 Principal Investigator, NCI UW National Cooperative Drug Discovery Group, University of Wisconsin-Madison
2004-2010 School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison
2004-2010 Charles M. Johnson Distinguished Chair, School of Pharmacy, University of Wisconsin-Madison
2001-2003 Associate Professor, School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison
1995-2001 Assistant Professor, Department of Chemistry, University of California, Davis
1991-1995 Postdoctoral Research Associate, University of Wisconsin-Madison

Awards & Professional Activities

1996-01, FIRST Award, NIH
1997-00, Searle Scholar, Searle Scholars Program
1998-03, CAREER Award, NSF
2000, Matt Suffness Award, American Society of Pharmacognosy
2001-06, Independent Scientist Award, NIH
2002, Jack L. Beal Award, American Society of Pharmacognosy
2011, Fellow, American Academy of Microbiology

2011, Fellow, American Association for the Advancement of Science
2015, Promega Biotechnology Research Award, American Society for Microbiology
2018, Charles Thom Award, Society of Industrial Microbiology and Biotechnology
2020, Outstanding Mentor Award, Society of Research Fellows, TSRI, Jupiter, FL

2002-16, Member, Editorial Board of J. Ind. Microbiol. Biotechnol.
2003-17, Member, Editorial Advisory Board of J. Nat. Prod.
2005-17, Member, Advisory Board of Mol. BioSyst.
2006-, Associate Editor, Acta Microbiologica Sinica
2009-, Member, Editorial Board of J. Antibiot.
2011, Guest Co-Editor, J. Antibiot. January issue in memory of C. Richard Hutchinson
2012, Guest Co-Editor, Curr. Opinion Chem. Biol. April issue on Biocatalysis and Biotransformation
2017-, Editor, J. Ind. Microbiol. Biotechnol.


Selected References

All Publications

281. Lohman, J. R.; Shen, B. (2020) The LnmK bifunctional acyltransferase/decarboxylase specifying (2R)-methylmalonyl-CoA and employing substrate-assisted catalysis for polyketide biosynthesis. Biochemistry 59:ASAP online.

280. Zhang, X.; King-Smith, E.; Dong, L.-B.; Yang, L-C. Rudolf, J. D.; Shen, B.; Renata, H. (2020) Divergent synthesis of complex diterpenes through a hybrid oxidative approach. Science 368:799-806.

279. Adhikari, A.; Teijaro, C.; Yan, X.; Chang, C.-Y.; Gui, C.; Yu-Chen Liu, Y.-C.; Crnovcic, I.; Yang, D.; Annaval, T.; Rader, C.; Shen, B. (2020) Characterization of TnmH as an O-methyltransferase revealing insights into tiancimycin biosynthesis and enabling a biocatalytic strategy to prepare antibody-tiancimycin conjugates. J. Med. Chem. 63:8432-8441.

278. Wang, Z.; Liu, X.; Peng, Y.; Su, M.; Zhu, S.; Pan, J.; Shen, B.; Duan, Y.; Huang, Y. (2020) Platensimycin-encapsulated liposomes or micelles as biosafe nanoantibiotics exhibited strong antibacterial activities against methicillin-resistant Staphylococcus aureus infection in mice. Mol. Pharm. 17:2451-2462.

277. Liu, X.; Wang, Z.; Feng, X.; Bai, E.; Xiong, Y.; Zhu, X.; Shen, B.; Duan, Y.; Huang, Y. (2020) Platensimycin-encapsulated poly(lactic-co-glycolic acid) and poly(amidoamine) dendrimers nanoparticles with enhanced anti-staphylococcal activity in vivo. Bioconj. Chem. 31:1425-1437.

276. Zhou, W.; Liang, H.; Qin, X.; Cao, D.; Zhu, X.; Ju, J.; Shen, B.; Duan, Y.; Huang, Y. (2020) The Isolation of pyrroloformamide congeners and characterization of their biosynthetic gene cluster. J. Nat. Prod. 83:202-209.

275.  Kalkreuter, E.; Pan, G.; Cepeda, A. J.; Shen, B. (2020) Targeting bacterial genomes for natural product discovery: opportunities, challenges, and strategies. Trends Pharmacol. Sci. 41:13-26.

274. Steele, A.; Kalkreuter, E.; Pan, G.; Meng, S.; Shen, B. (2020) “Hybrid Peptide-Polyketide Natural Product Biosynthesis” in Liu, H.-W.; Begley, T. P. (eds.) Comprehensive Natural Products III: Chemistry and Biology, vol 2, pp. 284-335. Elsevier.

273. Adhikari, A.; Teijaro, C. N.; Townsend, C. A.; Shen, B. (2020) “Biosynthesis of Enediyne Natural Products” in Liu, H.-W.; Begley, T. P. (eds.) Comprehensive Natural Products III: Chemistry and Biology, vol 1, 365-414. Elsevier.

272. Steele, A. D.; Teijaro, C. N.; Yang, D.; Shen, B. (2019) Leveraging a large microbial strain collection for natural product discovery. J. Biol. Chem. 294:16567-16576.

271. Wang, Z.; Wen, Z.; Liu, L.; Zhu, X.; Shen, B.; Yan, X.; Duan, Y.; Huang, Y. (2019) Yangpumicins F and G, enediyne congeners from Micromonospora yangpuensis DSM 45577. J. Nat. Prod. 82:2483-2488.

270. Liang, H.; Jiang, L.; Jiang, Q.; Shi, J.; Xiang, J.; Yan, X.; Zhu, X.; Zhao, L.; Shen, B.; Duan, Y.; Huang, Y. (2019) A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases. Environ Microbiol. 21:4270-4282.

269. Dong, L.-B.; Liu, Y.-C.; Cepeda, A. J.; Kalkreuter, E.; Deng, M.-R.; Rudolf, J. D.; Chang, C.; Joachimiak, A.; Phillips Jr, G. N.; Shen, B. (2019) Characterization and crystal structure of a nonheme diiron monooxygenase involved in platensimycin and platencin biosynthesis. J. Am. Chem. Soc. 141:12406-12412.

268. Deng, Y.; Weng, X.; Li, Y.; Su, M.; Wen, Z.; Ji, X.; Ren, N.; Shen, B.; Duan, Y.; Huang, Y. (2019) Late-stage functionalization of platensimycin leading to multiple analogues with improved antibacterial activity in vitro and in vivo. J. Med. Chem. 62:6682-6693.

267. Su, M.; Qiu, L.; Deng, Y.; Ruiz, C.; Rudolf, J. D.; Dong, L.-B.; Feng, X.; Cameron, M. D.; Shen, B.; Duan, Y.; Huang, Y. (2019) Evaluation of platensimycin and platensimycin‐inspired thioether analogues against methicillin‐resistant Staphylococcus aureus in topical and systemic infection mouse models. Mol. Pharmaceutics 16:3065-3071

266. Xu, Z.; Fang, S.-M.; Bakowski, M. A.; Rateb, M. E.; Yang, D.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; Hull, M.; McNamara, C. W.; Shen, B. (2019) Discovery of Kirromycins with Anti-Wolbachia Activity from Streptomyces sp. CB00686. ACS Chem. Biol. 14:1174-1182

265. Qiu, L.; Wen, Z.; Li, Y.; Tian, K.; Deng, Y.; Shen, B.; Duan, Y.; Huang, Y. (2019) Stereoselective functionalization of platensimycin and platencin by Sulfa‐Michael/Aldol reactions. Org. Biomol Chem. 17:4261-4272.

264. Dong, L.-B.; Zhang, X.; Rudolf, J. D.; Deng, M.-R.; Kalkreuter, E.; Cepeda, A. J.; Renata, H.; Shen, B. (2019) Cryptic and stereoselective hydroxylation, oxidation, and reduction in platensimycin and platencin biosynthesis. J. Am. Chem. Soc. 141:4043-4050.

263. Teijaro, C. N.; Ajeeth Adhikari, A.; Shen, B. (2019) Challenges and opportunities in microbial engineering for natural products. J. Ind. Microbiol. Biotechnol. 46:4043-4050 (SI on Natural Products Discovery and Development).

262. McAlpine, J.; et al.; Pauli, G. (2019) The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research. Nat. Prod. Rep. 36:35-107.

See Shen Laboratory website for complete list of publications (https://www.scripps.edu/shen/publications.html).

See MyBibliography for complete list of publications (

http://www.ncbi.nlm.nih.gov/sites/myncbi/ben.shen.1/bibliography/42110543/public/?sort=date&direction=ascending)

Google Scholar Citations (http://scholar.google.com/citations?hl=en&user=LNnZEd4AAAAJ ).


Links

Natural Products Discovery Center at Scripps Research